Tetracycline antibiotics are a kind of broad-spectrum antibiotics for oral use, which are generated by Actinomycete-Streptomyces fermentation. They have good pharmacological action against rickettsiales, many Gram-positive and Gram-negative bacteria, lymphogranuloma venereum pathogens, inclusion conjunctivitis pathogens and psittacosis pathogens.
The first tetracycline antibiotic is aureomycin extracted from Streptomyces aureofaciens in 1948, and then oxytetracycline, tetracycline and demeclocycline, which are all nature products have been developed successively. However, these drugs have high drug resistance and many side effects. Studies on the chemical structures of these compounds have been conducted later, and as a result, demethyl-tetracycline and dimethylamino-tetracycline have been synthesized. But the wide use of tetracyclines brings about more and more serious drug resistance of bacterium, which renders the use reduction of tetracycline antibiotics.
In the early 1990s, a new, third-generation tetracycline named as glycyclines were developed, and the representative drug was tigecylcine (GAR-936), which had broad antimicrobial spectrum. Tigecylcine has similar antibacterial activity with the prior tetracyclines, and further, due to efflux mechanism and ribosomal protection mechanisms, it has antibacterial activity even to the pathogens resistant against tetracyclines. However, tigecylcine can not be used orally, but only by intravenous drip for twice a day. Therefore, the use of tigecylcine is inconvenient and painful for patients. There is no oral-usable tigecylcine commercially available now.

The PCT application of WO2004/064728 has disclosed the compounds having structures as below, and studied the antibacterial activity thereof, but found they have poor antibacterial activity.

PTK-0796 is an oral-usable tetracycline antibiotic developed by Paratek Company, and it is being at phase III clinical trials for treating complex skin and skin soft-tissue infection. This drug may be administrated via injection or oral use once a day, and has broad antimicrobial spectrum. It has strong antibacterial activity to Grain-positive and Grain-negative bacteria, anaerobicbacteria, and atypical bacteria which are sensitive or resistance to many drugs. However, there are few tetracycline antibiotics similar with PTK-0796, and as such there are many limitations in the current clinic drug use.

Therefore, there is an insistent demand to develop new tetracycline antibiotics which have broad antimicrobial spectrum and strong antibacterial activity, and may be administrated for one time or orally, and may be easily synthesized and suitable for industrial production.